Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• utility of their reaction, the authors studied the one-pot conversion of the vinyl azides to 2H-azirines 161. The carboazidation reaction for the aryl alkynes was completed in a comparable amount of time. A myriad of different functionalized π-systems was tolerated by the reaction, demonstrating its

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• ][4][5][6][7][8][9][10][11][12][13]. Pyrroles with vicinal o-bromophenyl and heteroaryl substituents, which are readily accessible via reactions of the corresponding 2H-azirines and phenacylcycloiminium ylides [14][15][16][17][18][19], are excellent precursors for various fused aza-heteroaromatics via

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• preparation of 2H-azirines and their stereoselective transformation into highly functionalized NH-aziridines, starting from vinyl azides and organolithium compounds. The protocol has been developed using cyclopentyl methyl ether (CPME) as an environmentally benign solvent, resulting into a sustainable, safe

• and potentially automatable method for the synthesis of interesting strained compounds. Keywords: aziridines; 2H-azirines; flow chemistry; green chemistry; organolithium compounds; Introduction Since their conception in the early 1990s, Green Chemistry Principles (GCP) have been applied with

• olefins [13][14]. Aziridines are otherwise accessible from a variety of acyclic precursors [15][16][17], even stereoselectively [18][19][20], and through derivatization of 2H-azirines. The reactions using 2H-azirines as electrophiles proceed with several nitrogen, oxygen and sulfur nucleophiles, enabling

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• release approach, the Xiao group reported a synthesis of the pyrroles 35.3 in 2014 [153]. They can be accessed via a photocatalytic formal [3 + 2] cycloaddition of the 2H-azirines 35.1 and the alkynes 35.2 (Scheme 35). The use of Mes-Acr-Me+ (OD2) was successful due to its high reduction potential in the

• excited state, together with an intense absorption in the visible-light region. The transformation proceeds via the single-electron oxidation of 2H-azirines, forming a nitrogen-centered radical cation, which is prone to ring opening. The driving force of the ring strain release and irreversible ring

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• the [3 + 2]-cycloaddition of electron-poor alkynes and 2H-azirines [60]. The reaction is performed under blue LED irradiation and using acridinium salts as a photocatalyst (Scheme 15). With respect to 2H-azirine the scope of the reaction is demonstrated to be relatively broad, with aromatics

• ). The reaction uses 2H-azirines and aldehydes to access the functionalised heterocycles [61]. Unlike the pyrrole-forming reaction, this protocol requires an oxidising agent, DDQ, for the desired oxazole to be obtained. This means that access to the corresponding 2,5-oxazolines is also possible

Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination

• Jiyun Sun,
• Xiaohua Zhen,
• Huaibin Ge,
• Guangtao Zhang,
• Xuechan An and
• Yunfei Du

Beilstein J. Org. Chem. 2018, 14, 1452–1458, doi:10.3762/bjoc.14.123

• (Tianjin), Tianjin 300072, China 10.3762/bjoc.14.123 Abstract The reaction of enamine compounds with the Togni reagent in the presence of CuI afforded β-trifluoromethylated enamine intermediates, which were converted directly to biologically interesting trifluoromethylated 2H-azirines by an iodosobenzene

• potential anti-HIV drug bearing a NCF3 moiety. 2H-Azirines are a class of highly strained and reactive molecules containing a C–N double bond. The exclusive framework can be found in some natural products [43][44][45][46][47], which were shown to possess antibiotic activities [43][44]. Furthermore

• ) [56][57]. When the R2 substituent is alkyl or aryl, the corresponding substrates 2 were converted to a series of alkylated or arylated 2H-azirines 3 in the presence of phenyliodine diacetate (PIDA) in 1,2-dichloroethane (DCE) [56]. Alternatively, the treatment of β-unsubstituted enamine substrates (2

Continuous multistep synthesis of 2-(azidomethyl)oxazoles

• Thaís A. Rossa,
• Nícolas S. Suveges,
• Marcus M. Sá,
• David Cantillo and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2018, 14, 506–514, doi:10.3762/bjoc.14.36

• continuous-flow process. The general synthetic strategy involves a thermolysis of vinyl azides to generate azirines, which react with bromoacetyl bromide to provide 2-(bromomethyl)oxazoles. The latter compounds are versatile building blocks for nucleophilic displacement reactions as demonstrated by their

• subsequent treatment with NaN3 in aqueous medium to give azido oxazoles in good selectivity. Process integration enabled the synthesis of this useful moiety in short overall residence times (7 to 9 min) and in good overall yields. Keywords: azirines; continuous flow; heterocycles; oxazoles; process

• ]. An alternative approach consists of the ring expansion of azirines, which can be prepared from vinyl azides 1, by the reaction with carbonyl compounds. Substituted 2-acylazirines rearrange to oxazoles in the presence of bases [24][25][26]. In addition the light-mediated synthesis of oxazoles from

Investigation on the reactivity of α-azidochalcones with carboxylic acids: Formation of α-amido-1,3-diketones and highly substituted 2-(trifluoromethyl)oxazoles

• Kandasamy Rajaguru,
• Arumugam Mariappan,
• Rajendran Suresh,
• Periasamy Manivannan and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2015, 11, 2021–2028, doi:10.3762/bjoc.11.219

• temperature, it affords highly substituted 2-(trifluoromethyl)oxazoles. These flexible transformations proceed under solvent free conditions in good to excellent yields without any catalyst. Keywords: α-amido-1,3-diketones; α-azidochalcones; carboxylic acids; 2H-azirines; oxazoles; Introduction α

• reactive intermediate in several synthetic transformations [10][11][12][13][14][15]. The chemistry of 2H-azirines has been extensively explored because of its strained molecular structure, unique reactivity and synthetic applications [10][11][12][13][14][15][16][17][18][19][20][21][22]. α-Substituted 2H

• -azirines are impressive intermediates for the synthesis of various substituted heterocyclic compounds [23][24][25]. Nucleophiles can interact with the electrophilic carbon of the strained 2H-azirine rings and due to the ring strain in the three-membered 2H-azirine ring system A1, the electrophilic

Fe(II)/Et₃N-Relay-catalyzed domino reaction of isoxazoles with imidazolium salts in the synthesis of methyl 4-imidazolylpyrrole-2-carboxylates, its ylide and betaine derivatives

• Ekaterina E. Galenko,
• Olesya A. Tomashenko,
• Alexander F. Khlebnikov,
• Mikhail S. Novikov and
• Taras L. Panikorovskii

Beilstein J. Org. Chem. 2015, 11, 1732–1740, doi:10.3762/bjoc.11.189

• -imidazoles based on the formation of a pyrrole ring via the reaction of 2H-azirines with 1-alkyl-3-phenacyl-1H-imidazolium bromides [29], in which one example of the synthesis of ethyl 4-imidazolylpyrrole-2-carboxylate from ethyl 3-methyl-2H-azirine-2-carboxylate was described. Earlier it was found that

• according to Scheme 2, whereby excluding the isolation of often unstable 2H-azirines [34]. Results and Discussion The synthetic scheme (Scheme 2) implies an implementation of all stages (1: generation of azirine 8 from isoxazole 7 under FeCl2 catalysis; 2: formation of phenacylimidazolium ylide 10 induced

Azirinium ylides from α-diazoketones and 2H-azirines on the route to 2H-1,4-oxazines: three-membered ring opening vs 1,5-cyclization

• Nikolai V. Rostovskii,
• Mikhail S. Novikov,
• Alexander F. Khlebnikov,
• Galina L. Starova and
• Margarita S. Avdontseva

Beilstein J. Org. Chem. 2015, 11, 302–312, doi:10.3762/bjoc.11.35

• , Universitetskaya nab. 7–9, 199034 St. Petersburg, Russia 10.3762/bjoc.11.35 Abstract Strained azirinium ylides derived from 2H-azirines and α-diazoketones under Rh(II)-catalysis can undergo either irreversible ring opening across the N–C2 bond to 2-azabuta-1,3-dienes that further cyclize to 2H-1,4-oxazines or

• reversibly undergo a 1,5-cyclization to dihydroazireno[2,1-b]oxazoles. Dihydroazireno[2,1-b]oxazoles derived from 3-aryl-2H-azirines and 3-diazoacetylacetone or ethyl diazoacetoacetate are able to cycloadd to acetyl(methyl)ketene generated from 3-diazoacetylacetone under Rh(II) catalysis to give 4,6-dioxa-1

• ring opening into atropoisomeric oxazolium betaines and cyclization. Azirinium ylides generated from 2,3-di- and 2,2,3-triaryl-substituted azirines give rise to only 2-azabuta-1,3-dienes and/or 2H-1,4-oxazines. Keywords: 2-azabuta-1,3-dienes; azirines; diazo compounds; nitrogen ylides; 2H-1,4-oxazines

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• synthetic approach to derivatives of 2H-1,3-oxazines via a Rh2(OAc)4-catalyzed reaction of diazo esters with 2-acyl-2H-azirines F. This reaction involves the intermediate formation of azirinium ylides G, their transformation into 1-oxa-5-azahexa-1,3,5-triene D, and finally the 6π-electrocyclization of the

• latter to give oxazine E (Scheme 2) [10][11]. Azirinium ylides G, formed by the reaction of azirines F with carbenoids, can transform into (3Z)- and (3E)-1-oxa-5-azahexa-1,3,5-triene D, but only the former can cyclize into 1,3-oxazines E. In contrast, the reaction of isoxazoles with carbenoids results in

• diazo esters. Reaction of azirines 1a with diazo compounds 2a–c without a catalyst. Synthesis of oxazines 3a–m. Synthesis of 1-oxa-5-azahexa-1,3,5-trienes 4a–f. Supporting Information Supporting Information File 338: Detailed experimental procedures including characterization data for all synthesized

Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Viktoriia V. Pakalnis,
• Roman O. Iakovenko and
• Dmitry S. Yufit

Beilstein J. Org. Chem. 2014, 10, 784–793, doi:10.3762/bjoc.10.74

• 10.3762/bjoc.10.74 Abstract 3-Aryl-2H-azirines react with acylketenes, generated by thermolysis of 5-arylfuran-2,3-diones, to give bridged 5,7-dioxa-1-azabicyclo[4.4.1]undeca-3,8-diene-2,10-diones and/or ortho-fused 6,6a,12,12a-tetrahydrobis[1,3]oxazino[3,2-a:3′,2′-d]pyrazine-4,10-diones. The latter

• compounds, with a new heterocyclic skeleton, are the result of the coupling of two molecules of azirine and two molecules of acylketene and can be prepared only from 3-aryl-2H-azirines having no electron-withdrawing groups in the aryl substituent. Calculations at the DFT B3LYP/6-31G(d) level for the various

• routes of bis[1,3]oxazino[3,2-a:3′,2′-d]pyrazine skeleton formation revealed a new domino reaction of 3-aryl-2H-azirines occurring in the presence of furandiones: acid-catalyzed dimerization to dihydropyrazine followed by consecutive cycloaddition of the latter to two molecules of acylketenes. Keywords

[3 + 2]-Cycloadditions of nitrile ylides after photoactivation of vinyl azides under flow conditions

• Stephan Cludius-Brandt,
• Lukas Kupracz and
• Andreas Kirschning

Beilstein J. Org. Chem. 2013, 9, 1745–1750, doi:10.3762/bjoc.9.201

• Stephan Cludius-Brandt Lukas Kupracz Andreas Kirschning Institute of Organic Chemistry, Leibniz University Hannover, Schneiderberg 1b, 30167 Hannover, Germany 10.3762/bjoc.9.201 Abstract The photodenitrogenation of vinyl azides to 2H-azirines by using a photoflow reactor is reported and compared

• with thermal formation of 2H-azirines. Photochemically, the ring of the 2H-azirines was opened to yield the nitrile ylides, which underwent a [3 + 2]-cycloaddition with 1,3-dipolarophiles. When diisopropyl azodicarboxylate serves as the dipolarophile, 1,3,4-triazoles become directly accessible starting

• from the corresponding vinyl azide. Keywords: azirines; cycloaddition; flow chemistry; flow reactors; inductive heating; nitrile ylides; photochemistry; vinyl azides; Introduction Recently, photochemistry has seen a renaissance despite the fact that under batch conditions specialized reaction vessels

Multistep flow synthesis of vinyl azides and their use in the copper-catalyzed Huisgen-type cycloaddition under inductive-heating conditions

• Lukas Kupracz,
• Jan Hartwig,
• Jens Wegner,
• Sascha Ceylan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2011, 7, 1441–1448, doi:10.3762/bjoc.7.168

• , vinyl azides can be converted into the corresponding 2H-azirines by thermolysis or alternatively by photolysis [5]. The highly reactive azirines can further react as dipolarophiles, dienophiles, electrophiles or nucleophiles [6] thereby accessing oxazoles and isoxazoles [7]. In addition, 2H-azirines

Photocycloaddition of aromatic and aliphatic aldehydes to isoxazoles: Cycloaddition reactivity and stability studies

• Axel G. Griesbeck,
• Marco Franke,
• Jörg Neudörfl and
• Hidehiro Kotaka

Beilstein J. Org. Chem. 2011, 7, 127–134, doi:10.3762/bjoc.7.18

• the presence of benzaldehyde. Instead, a reaction could be observed which also occurred both in the presence of a tenfold excess of aldehyde or without any aldehyde. This reaction was identified as the intramolecular ring contraction of 7f–h to yield the corresponding azirines 8a–c (Scheme 4) [16